Can donor splice site recognition occur without the involvement of U1 snRNP?

Raponi, Michela; Baralle, Diana

doi:10.1042/bst0360548

Cited by 9 publications

(6 citation statements)

References 15 publications

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“…Recently, Raponi and Baralle (34) proposed a possibility that U1-independent splicing could be disrupted by some disease-causing mutations in the 5′ splice site.…”

Section: Resultsmentioning

confidence: 99%

U1-independent pre-mRNA splicing contributes to the regulation of alternative splicing

Fukumura¹,

Taniguchi²,

Sakamoto³

et al. 2009

Nucleic Acids Research

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U1 snRNP plays a crucial role in the 5′ splice site recognition during splicing. Here we report the first example of naturally occurring U1-independent U2-type splicing in humans. The U1 components were not included in the pre-spliceosomal E complex formed on the human F1γ (hF1γ) intron 9 in vitro. Moreover, hF1γ intron 9 was efficiently spliced even in U1-disrupted Xenopus oocytes as well as in U1-inactivated HeLa nuclear extracts. Finally, hF1γ exon 9 skipping induced by an alternative splicing regulator Fox-1 was impaired when intron 9 was changed to the U1-dependent one. Our results suggest that U1-independent splicing contributes to the regulation of alternative splicing of a class of pre-mRNAs.

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“…Recently, Raponi and Baralle (34) proposed a possibility that U1-independent splicing could be disrupted by some disease-causing mutations in the 5′ splice site.…”

Section: Resultsmentioning

confidence: 99%

U1-independent pre-mRNA splicing contributes to the regulation of alternative splicing

Fukumura¹,

Taniguchi²,

Sakamoto³

et al. 2009

Nucleic Acids Research

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“…Complementarity to U1 snRNA plays a pivotal role in 5 0 ss selection [Seraphin et al, 1988;Siliciano and Guthrie, 1988;Zhuang and Weiner, 1986] even though cases of U1-independent splicing through an U6-dependent mechanism have been documented [Crispino et al, 1994;Raponi and Baralle, 2008]. Then it is reasonable to hypothesize that the compensatory changes observed in native 5 0 ss are intended to maintain the number of basepairs between U1 snRNA and 5 0 ss above the minimum.…”

Section: Discussionmentioning

confidence: 96%

Sequence contexts that determine the pathogenicity of base substitutions at position +3 of donor splice-sites

et al. 2009

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Variations at position +3 of 5' splice-sites (5'ss) are reported to induce aberrant splicing in some cases but not in others suggesting that the overall nucleotidic environment can dictate the extent to which 5'ss are correctly selected. Functional studies of three variations identified in donor splice-sites of USH2A and PCDH15 genes sustain this assumption. To gain insights into this question, we compared the nucleotidic context of U2-dependent 5'ss naturally deviated (+3G,+3C, or+3T) from the+3A consensus with 5'ss for which a +3 variation (A>G, A>C, or A>T) was shown to induce aberrant splicing. Statistical differences were found between the two datasets, highlighting the role of one peculiar position in each context (+3G/+4A; +3C/-1G; and +3T/-1G). We provided experimental support to the biostatistical results through the analysis of a series of artificial mutants in reporter minigenes. Moreover, different 5' end-mutated U1 snRNA expression plasmids were used to investigate the importance of the position +3 and of the two identified compensatory positions -1 and +4 in the recognition of 5'ss by the U1 snRNP. Overall, our findings establish general properties useful to molecular geneticists to identify nucleotide substitutions at position +3 that are more likely to alter splicing.

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“…2), which could influence the phenotype. The non‐coding RNA gene, U1 , codes for a small nuclear RNA that is part of the spliceosome and thus essential for correct pre‐mRNA splicing for most pre‐mRNAs [Raponi and Baralle, 2008]. There are multiple copies of this gene throughout the human genome (UCSC Human Genome Browser, hg18), which can be found as isolated genes or in clusters, for example, in the chromosome 1p36.13 and 1q21.1 regions.…”

Section: Discussionmentioning

confidence: 99%

UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients

Leeuw

Bulk

Green

et al. 2010

American J of Med Genetics Pt A

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We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present in patients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck.

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Can donor splice site recognition occur without the involvement of U1 snRNP?

Cited by 9 publications

References 15 publications

U1-independent pre-mRNA splicing contributes to the regulation of alternative splicing

U1-independent pre-mRNA splicing contributes to the regulation of alternative splicing

Sequence contexts that determine the pathogenicity of base substitutions at position +3 of donor splice-sites

UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients

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